Progress in autoimmune epileptic encephalitis

Purpose of review Autoimmune epileptic encephalopathy is a potentially treatable neurological syndrome characterized by the coexistence of a neuronal antibody in serum and, often, cerebrospinal fluid. Patients present with combinations of seizures, neuropsychiatric features, movement disorder, and cognitive decline, but some patients have isolated seizures either at first presentation or during their illness. This review summarizes our current understanding of the roles of specific neuronal antibodies in epilepsy-related syndromes and aims to aid the clinician in diagnosis and treatment. Recent findings Antigen discovery methods in three neuroimmunology centres independently identified antibodies to different subunits of the γ amino butyric acid-A receptor; high levels of these antibodies were found mainly in patients with severe refractory seizures. These and other antibodies were also found in a proportion (<10%) of children and adults with epilepsy. A clinical study comparing immunotherapy in patients with autoantibodies or without an identified target antigen found neuroinflammatory features were predictive of a therapeutic response. New in-vitro and in-vivo studies, and spontaneous animal models, have confirmed the pathogenicity and epileptogenicity of neuronal antibodies and their relevance to other mammals. Summary Neuronal antibodies are an important cause of autoimmune epileptic encephalopathy, early recognition is important as there may be an underlying tumour, and early treatment is associated with a better outcome. In the absence of an antibody, the clinician should adopt a pragmatic approach and consider a trial of immunotherapy when other causes have been excluded

Tree diversity and above-ground biomass in the South America Cerrado biome and their conservation implications

Less than half of the original two million square kilometers of the Cerrado vegetation remains standing, and there are still many uncertainties as to how to conserve and prioritize remaining areas effectively. A key limitation is the continuing lack of geographically-extensive evaluation of ecosystem-level properties across the biome. Here we sought to address this gap by comparing the woody vegetation of the typical cerrado of the Cerrado–Amazonia Transition with that of the core area of the Cerrado in terms of both tree diversity and vegetation biomass. We used 21 one-hectare plots in the transition and 18 in the core to compare key structural parameters (tree height, basal area, and above-ground biomass), and diversity metrics between the regions. We also evaluated the effects of temperature and precipitation on biomass, as well as explored the species diversity versus biomass relationship. We found, for the first time, both that the typical cerrado at the transition holds substantially more biomass than at the core, and that higher temperature and greater precipitation can explain this difference. By contrast, plot-level alpha diversity was almost identical in the two regions. Finally, contrary to some theoretical expectations, we found no positive relationship between species diversity and biomass for the Cerrado woody vegetation. This has implications for the development of effective conservation measures, given that areas with high biomass and importance for the compensation of greenhouse gas emissions are often not those with the greatest diversity

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Measurement of the Pseudorapidity and Centrality Dependence of the Transverse Energy Density in Pb-Pb Collisions at √sNN=2.76 TeV

The transverse energy (E-T) in Pb-Pb collisions at 2.76 TeV nucleon-nucleon center-of-mass energy (root s(NN)) has been measured over a broad range of pseudorapidity (eta) and collision centrality by using the CMS detector at the LHC. The transverse energy density per unit pseudorapidity (dE(T)/d eta) increases faster with collision energy than the charged particle multiplicity. This implies that the mean energy per particle is increasing with collision energy. At all pseudorapidities, the transverse energy per participating nucleon increases with the centrality of the collision. The ratio of transverse energy per unit pseudorapidity in peripheral to central collisions varies significantly as the pseudorapidity increases from eta = 0 to vertical bar eta vertical bar = 5.0. For the 5% most central collisions, the energy density per unit volume is estimated to be about 14 GeV/fm(3) at a time of 1 fm/c after the collision. This is about 100 times larger than normal nuclear matter density and a factor of 2.6 times higher than the energy density reported at root s(NN) = 200 GeV at the Relativistic Heavy Ion Collider

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Indications of suppression of excited Υ states in Pb-Pb collisions at √sNN = 2.76TeV

This is the pre-print version of the Published Article which can be accessed from the link below.A comparison of the relative yields of Υ resonances in the μ+μ- decay channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of 2.76 TeV is performed with data collected with the CMS detector at the LHC. Using muons of transverse momentum above 4  GeV/c and pseudorapidity below 2.4, the double ratio of the Υ(2S) and Υ(3S) excited states to the Υ(1S) ground state in Pb-Pb and pp collisions, [Υ(2S+3S)/Υ(1S)]Pb-Pb/[Υ(2S+3S)/Υ(1S)]pp, is found to be 0.31-0.15+0.19(stat)±0.03(syst). The probability to obtain the measured value, or lower, if the true double ratio is unity, is calculated to be less than 1%

Measurement of the t-channel single top quark production cross section in pp collisions at √s = 7TeV

This is the pre-print version of the Published Article which can be accessed from the link below.Electroweak production of the top quark is measured for the first time in pp collisions at √s=7  TeV, using a data set collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36  pb-1. With an event selection optimized for t-channel production, two complementary analyses are performed. The first one exploits the special angular properties of the signal, together with background estimates from the data. The second approach uses a multivariate analysis technique to probe the compatibility with signal topology expected from electroweak top-quark production. The combined measurement of the cross section is 83.6±29.8(stat+syst)±3.3(lumi)  pb, consistent with the standard model expectation

Search for same-sign top-quark pair production at root s=7 TeV and limits on flavour changing neutral currents in the top sector

An inclusive search for same-sign top-quark pair production in pp collisions at root s = 7 TeV is performed using a data sample recorded with the CMS detector in 2010, corresponding to an integrated luminosity of 35 pb(-1). This analysis is motivated by recent studies of p (p) over bar -> t (t) over bar reporting mass-dependent forward-backward asymmetries larger than expected from the standard model. These asymmetries could be due to Flavor Changing Neutral Currents (FCNC) in the top sector induced by t -channel exchange of a massive neutral vector boson (Z'). Models with such a Z' also predict enhancement of same-sign top-pair production in pp or pp collisions. Limits are set as a function of the Z' mass and its couplings to u and t quarks. These limits disfavour the FCNC interpretation of the Tevatron results

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation